Abstract: Objective To investigate the effect of scutellarin(STR) on the proliferation and migration of human prostate cancer cell line (PC-3) and its underlying mechanism. Methods PC-3 cells were divided into low-dose STR group, medium-dose STR group, high-dose STR group, colivelin (STAT3 activator) group, high-dose STR+colivelin group and control group. CCK-8 assay and colony formation experiments were applied to detect cell proliferation; Scratch experiment was applied to detect cell migration; Transmission electron microscopy was applied to observe the mitochondrial ultrastructure of PC-3 cells. The intracellular free Fe²⁺, malondialdehyde (MDA) content and reactive oxygen species (ROS) levels were detected by colorimetric method; RT-qPCR was applied to detect the mRNA expression of member 11 of solute vector family (SLC7A11), proliferating cell nuclear antigen(PCNA) and matrix metalloproteinase-9 (MMP-9) in cells; Western blot was used to detected p-STAT3 and GPX4 proteins in cells. Results Compared to control group, the mitochondrial structure of PC-3 cells in the low-dose STR group, medium-dose STR group and high-dose STR group was significantly disrupted. The A₄₅₀ value, colony formation rate, scratch healing rate, PCNA, SLC7A11, MMP-9 mRNA expression, and p-STAT3, GPX4 protein all reduced. While Fe²⁺, MDA content, and that ROS level increased with dose-dependent way(P＜0.05). Compared with control group, the destruction of mitochondrial structure in cells from colivelin group improved; The A₄₅₀ value, colony formation rate, scratch healing rate, PCNA, SLC7A11, MMP-9 mRNA expression and p-STAT3, GPX4 protein all increased, while Fe²⁺ MDA content, and ROS level decreased (P＜0.05). Compared with high-dose STR group, the damage of mitochondrial structure in PC-3 cells in the high-dose STR+colivelin group was reduced. The A₄₅₀ value, colony formation rate, scratch healing rate, PCNA, SLC7A11, MMP-9 mRNA expression, and p-STAT3, GPX4 protein increased, while Fe²⁺, MDA content and ROS level decreased (P＜0.05). Conclusions The mechanism by of STR reducing proliferation and migration of prostate cancer cells is potentially related to the inhibition of STAT3/GPX4 pathway.

Key words: scutellarin, prostate cancer, signal transducer and activator of transcription 3/glutathione peroxidase 4 signaling pathway, ferroptosis, proliferation